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Targeted next-generation sequencing panel (TruSight Tumor 170) in diffuse glioma: a single institutional experience of 135 cases

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Abstract

Purpose

The TruSight Tumor 170 (TST-170) panel consists of a DNA workflow for the identification of single-nucleotide variants, small insertions and deletions, and copy number variation, as well as a panel of 55 genes for a RNA workflow for the identification of splice variants and gene fusions. To date, the application of TST-170 in diffuse gliomas (DGs) has not been described.

Methods

We analyzed 135 samples of DG, which were diagnosed by WHO criteria based on histological features and conventional molecular tests including immunostaining, 1p/19q FISH, and analysis of MGMT methylation and TERT promoter mutation.

Results

A total of 135 cases consisted of 38 IDH-mutant [17 astrocytoma (AC), 13 oligodendroglioma (OD) and eight glioblastoma (GBM)], 87 IDH-wildtype (six AC, three OD and 78 GBM), and 10 diffuse midline glioma, H3K27M-mutant. DNA analysis enabled the detection of all mutations identified in these samples by conventional techniques, and the results were highly comparable to the known mutations in each subtype. RNA analysis detected four fusion genes including PTPRZ1–MET, FGFR3–TACC3, FAM131B–BRAF, and RET–CCDC6 and one splicing variant (EGFR vIII mutant). Clustered copy number loss in 1p and 19q loci genes were detected in 1p/19q-codeleted OD.

Conclusions

The application of TST-170 panel based NGS in clinical and laboratory setting is expected to improve diagnostic accuracy and prognostication. Most benefits are expected in IDH-wildtype DG, a group of genetically heterogenous tumors harboring DNA sequence changes, copy number alterations, and fusions in a large number of oncogenes and tumor suppressor genes.

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Funding

This work was supported by the Brain Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (Grant No. 2016M3C7A1913844).

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Authors and Affiliations

  1. Department of Pathology, Kyung Hee University School of Medicine, Seoul, Republic of Korea

    Kiyong Na

  2. Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea

    Kiyong Na, Hyun-Soo Kim, Hyo Sup Shim & Se Hoon Kim

  3. Department of Neurosurgery, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea

    Jong Hee Chang & Seok-Gu Kang

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  1. Kiyong Na
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Correspondence to Se Hoon Kim.

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Na, K., Kim, HS., Shim, H.S. et al. Targeted next-generation sequencing panel (TruSight Tumor 170) in diffuse glioma: a single institutional experience of 135 cases. J Neurooncol 142, 445–454 (2019). https://doi.org/10.1007/s11060-019-03114-1

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